Modulation of immunogenicity of poly(sarcosine) displayed on various nanoparticle surfaces due to different physical properties

Poly(sarcosine) displayed on polymeric micelle is reported to trigger a T cell‐independent type2 reaction with B1a cells in the mice to produce IgM and IgG3 antibodies. In addition to polymeric micelle, three kinds of vesicles displaying poly(sarcosine) on surface were prepared here to evaluate the amounts and avidities of IgM and IgG3, which were produced in mice, to correlate them with physical properties of the molecular assemblies. The largest amount of IgM was produced after twice administrations of a polymeric micelle of 35 nm diameter ( G1 ). On the other hand, the production amount of IgG3 became the largest after twice administrations of G3 (vesicle of 229 nm diameter) or G4 (vesicle of 85 nm diameter). The augmented avidity of IgG3 after the twice administrations compared with that at the single administration was the highest with G3 . These differences in immune responses are discussed in terms of surface density of poly(sarcosine) chains, nanoparticle size, hydrophobic component of poly(L‐lactic acid) or (Leu‐ or Val‐Aib)_n, and membrane elasticity of the nanoparticles. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.     

CXCR4 is a major chemokine receptor on glioma cells and mediates their survival

Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. We addressed whether and which chemokines may be important promoters of the growth of the incurable brain neoplasm, malignant gliomas. Analyses of 16 human glioma lines for the expression of chemokine receptors belonging to the CXCR and CCR series revealed low to negligible levels of all receptors, with the exception of CXCR4 that was expressed by 13 of 16 lines. All six resected human glioma specimens showed similarly high CXCR4 expression. The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium. SDF-1 also mediated glioma chemotaxis, in accordance with this better known role of chemokines. We conclude that glioma cells express a predominant chemokine receptor, CXCR4, and that this functions to regulate survival in part through activating pathways such as Akt.     

New evidence that nuclear import of endogenous beta-catenin is LEF-1 dependent, while LEF-1 independent import of exogenous beta-catenin leads to nuclear abnormalities

The once accepted idea that LEF-1 transports beta-catenin into nuclei has recently been challenged by experiments using exogenous beta-catenin. Here, we investigated the effects of beta-catenin and LEF-1 on nuclear import of beta-catenin using different combinations of exogenous and endogenous molecules over longer lengths of time than previously studied. Nuclear beta-catenin is not detectable in corneal fibroblasts and epithelia or NIH 3T3 and MDCK cells. In LEF-1 transfections, we show that the B-box of LEF-1 is required to move cytoplasmic endogenous beta-catenin into the nuclei of such cells, proving that LEF-1 does transport endogenous beta-catenin into nuclei. Moreover, transfection of uveal melanoma cells with B-box deficient LEF-1 inhibits nuclear import of beta-catenin by endogenous LEF-1. However, the movement of overexpressed exogenous beta-catenin into nuclei is unaffected by the presence or absence of LEF-1 and forms abnormal nuclear aggregates that are a prelude to subsequent apoptosis. We conclude that nuclear transport of exogenous beta-catenin independently of LEF-1 has questionable physiological significance.     

Suppression of hepatic fatty acid synthase by feeding alpha-linolenic acid rich perilla oil lowers plasma triacylglycerol level in rats

This study was performed to determine the effects of dietary perilla oil, a n-3 alpha-linolenic acid (ALA) source, on hepatic lipogenesis as a possible mechanism of lowering triacylglycerol (TG) levels. Male Sprague-Dawley rats were trained for a 3-hour feeding protocol and fed one of five semipurified diets as follows: 1% (w/w) corn oil control diet, or one of four diets supplemented with 10% each of beef tallow, corn oil, perilla oil, and fish oil. Two separate experiments were performed to compare the effects of feeding periods, 4 weeks and 4 days. Hepatic and plasma TG levels were decreased in rats fed perilla oil and fish oil diets, compared with corn oil and beef tallow diets. The activities of hepatic lipogenic enzymes such as fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase, and malic enzyme were suppressed in the fish oil, perilla oil, and corn oil-fed groups, and the effect was the most significant in the fish oil-fed group. Also, the activities of glycolytic enzymes, glucokinase, and L-pyruvate kinase showed the similar trend as that of lipogenic enzymes. The activity of FAS, the key regulatory enzyme in lipogenesis, was positively correlated with hepatic and plasma TG levels and reduced significantly in the perilla oil-fed group compared with corn oil-fed group. In addition, the FAS activity was negatively correlated with the hepatic microsomal content of EPA and DHA. In conclusion, suppression of FAS plays a significant role in the hypolipidemic effects observed in rats fed ALA rich perilla oil and these effects were associated with the increase of hepatic microsomal EPA and DHA contents.     

化学灭鼠对长江流域农区鼠类群落结构的影响

长江流域农业生态系统内,农田的主要害鼠为褐家鼠、黑线姬鼠、黄胸鼠、小家鼠、东方田鼠等,各地的鼠种组成有所不同,优势鼠种也因地而异。农房区的害鼠主要有褐家鼠、小家鼠、黄胸鼠3种,优势鼠种各地亦有区别。但经化学灭鼠后的残留鼠种却有一共同的特点：灭鼠活动对褐家鼠种群的打击最大,灭后褐家鼠种群密度下降幅度最大;相对而言,小型鼠黑线姬鼠（农田区）与小家鼠（农舍区）及栖息在房屋上层的黄胸鼠,常成为灭鼠活动后的主要残留鼠种。化学灭鼠后鼠类群落结构比灭前都要发生较大的变化,这种差别中维持3a左右,但经过3-4a左右的恢复后,灭鼠区的鼠类群落组成与相似环境内自然演变区的已达基本一致。可见,化学灭鼠活动可以在短时间内对害鼠群落结构造成重大的影响,从长期看,害鼠群落的演变有着自身的规律,灭鼠后一定时期,鼠类群落结构将恢复到环境所决定的水平,灭鼠区的长期演替结构仍与相似环境内未灭鼠区的一样。     

干扰素通路调控与自身免疫疾病

干扰素信号通路是细胞抵抗病原微生物侵染的重要防线。通过识别病源相关模式分子、激活下游通路,干扰素的表达被显著上调并分泌于细胞外,作用于自身和周围细胞,引发众多下游基因的转录激活。这些基因产物直接参与抗侵染过程或调控机体免疫反应。干扰素信号通路需要被正确调控,其异常激活会导致炎症和自身免疫疾病的发生。正确地识别“自己”和“非己”分子是首要的一步。鉴于干扰素通路所抵抗的微生物侵染中,核酸分子是重要的免疫原性分子,内源性核酸分子的代谢调控显得尤为重要。细胞编码一系列参与核酸代谢的酶,这些蛋白质功能的发挥对保持细胞核酸稳态至关重要。以单基因突变引发的自身免疫疾病Aicardi-Goutières综合征为例,目前发现9种基因可突变致病,均来自DNA代谢相关的和RNA代谢相关的基因。尽管这9种基因突变都导致干扰素通路的异常激活,但中间所依赖的参与蛋白并不相同。可见,同样症状的疾病,其致病机理也可能不同,这也将影响有效治疗方案的确定,凸显基因检测在诊治自身免疫疾病中的必要性。本综述通过阐述细胞内环境稳态对干扰素通路正确识别“自己”和“非己”的重要作用,帮助理解自身免疫疾病的发病机理。     

基于光合系统参数建立马铃薯耐荫性综合评价体系

为构建便捷的马铃薯(Solanum tuberosum)耐荫性综合评价体系并发掘耐荫种质, 以35个马铃薯品种(系)为实验材料, 测定块茎膨大期遮荫下植株叶片叶绿素含量、光合能力和叶绿素荧光等光合参数及收获后块茎单株产量和淀粉含量等指标。根据耐荫系数, 利用主成分分析法、隶属函数法、聚类分析法和逐步回归分析法进行综合评价。通过主成分分析将马铃薯耐荫性相关的13个单项光合指标转换为6个综合指标, 代表了全部信息的87.51%。以此计算各种质的隶属函数值, 并以主成分的贡献率进行加权, 最终获得所用材料耐荫性的综合评价值(D值)。根据D值聚类分析结果将35个马铃薯分为4类, 其中Eshu10和Lishu6分别为耐荫性最强和最弱的品种。通过逐步回归分析建立了马铃薯耐荫性评价数学模型: D=0.060+0.106G_s+0.214qP+0.143NPQ。同时, 用该评价体系鉴定为耐荫性强的品种(系)在遮荫后其产量和/或淀粉含量等指标减幅均低于耐荫性弱的种质, 表明该评价体系可用于快速评价和预测马铃薯种质的耐荫性。     

通过染色体外同源重组建立乳腺中表达外源基因的转基因小鼠

为研究染色体外重组方法在创建转基因动物中的应用,选取牛asl酪蛋白基因的5′及3′侧翼区和氯霉素乙酰化酶编码区,构建了两个具有3 kb相互重叠的融合基因.将这两个DNA片段末端脱磷酸后,以摩尔比1:1的比例混合,通过显微注射导入小鼠受精原核,最后获得了11个品系的转基因小鼠.对其中10个品系的小鼠的整合分析表明,所注射的两个DNA片段均发生了染色体外同源重组,而且除了 1个品系的小鼠丢失了大约1kb的序列外,其余品系小鼠的重组产物与预想的结构符合.在当代和后代的转基因小鼠乳汁中均可测到氯霉素乙酰化酶的活性.这表明融合基因在转基因小鼠乳腺中得到表达和分泌,也说明显微共注射两个相互重叠的基因片段是建立转基因动物的一个可行途径.     

35种鲜花的抗氧化活性

采用了Fe^2 诱发的脂蛋白PUFA过氧化、H2O2诱导的RBC溶血和紫外线（UV）诱发的RBC溶血等3个体外抗氧化实验体系,对映山红（Rhododendron simsii Planch.)等35种鲜花的抗氧化活性进行了测定和比较。结果表明,在所测定的35种鲜花中,4种杜鹃属（Rhododendron L.)植物的花勒抗氧化活性最强。一定浓度白杜鹃[R.mucronatum (Blume)G.Don]花蕾提取液的抗Fe^2 诱发的脂蛋白PUFA过氧化活性明显高于维生素C。